tbuckley/cabot-search huggingface dataset:
Preeclampsia and Long-Term Risk of Venous Thromboembolism
Authors: Eva Havers-Borgersen, Jawad H. Butt, Marianne Johansen, Olav Bjørn Petersen, Charlotte Kvist Ekelund, Line Rode, Jonas Bjerring Olesen, Lars Køber, Emil L. Fosbøl
Journal: JAMA Network Open (2023)

Importance As venous thromboembolism (VTE) remains one of the leading causes of maternal mortality, identifying women at increased risk of VTE is of great importance. Preeclampsia is a pregnancy-induced hypertensive disorder with generalized endothelial dysfunction. Some studies suggest that preeclampsia is associated with an increased risk of VTE, but much controversy exists. Objective To examine the association between preeclampsia and the risk of VTE during pregnancy, during the puerperium, and after the puerperium. Design, Setting, and Participants This observational cohort study used Danish nationwide registries to identify all eligible primiparous women who gave birth in Denmark from January 1, 1997, to December 31, 2016. The women were followed up from primiparous pregnancy to incident VTE, emigration, death, or the end of the study (December 31, 2016). Statistical analyses were carried out from January to May 2023. Exposure Preeclampsia during primiparous pregnancy. Main Outcomes and Measure The main outcome was incident VTE, and the secondary outcome was all-cause mortality. Results A total of 522 545 primiparous women (median age, 28 years [IQR, 25-31 years]) were included, and 23 330 (4.5%) received a diagnosis of preeclampsia. Women with preeclampsia were of similar age to women without preeclampsia but had a higher burden of comorbidities. During a median follow-up of 10.2 years (IQR, 5.2-15.4 years), preeclampsia was associated with a higher incidence of VTE compared with no preeclampsia (incidence rate, 1.23 [95% CI, 1.10-1.38] vs 0.85 [95% CI, 0.82-0.87] per 1000 patient-years, corresponding to an unadjusted hazard ratio [HR] of 1.45 [95% CI, 1.29-1.63] and an adjusted HR of 1.43 [95% CI, 1.27-1.61]). When stratified according to the subcategories of VTE, preeclampsia was associated with an increased rate of deep vein thrombosis (unadjusted HR, 1.51 [95% CI, 1.32-1.72] and adjusted HR, 1.49 [95% CI, 1.31-1.70]) as well as pulmonary embolism (unadjusted HR, 1.39 [95% CI, 1.09-1.76]; adjusted HR, 1.36 [95% CI, 1.08-1.73]). These findings held true in landmark analyses during pregnancy, during the puerperium, and after the puerperium. Conclusions and Relevance This cohort study suggests that preeclampsia was associated with a significantly increased risk of VTE during pregnancy, during the puerperium, and after the puerperium, even after thorough adjustment. Future studies should address how to improve the clinical management of women with a history of preeclampsia to prevent VTE.
Statin Use, Cholesterol Level, and Mortality Among Females With Breast Cancer
Authors: Mika O. Murto, Niklas Simolin, Otso Arponen, Aino Siltari, Miia Artama, Kala Visvanathan, Arja Jukkola, Teemu J. Murtola
Journal: JAMA Network Open (2023)

Importance Several studies have reported an association between the use of statins and breast cancer (BC) mortality. However, most of these studies did not take into account the underlying cholesterol level. Objective To investigate the association between serum cholesterol, statin use, and BC mortality. Design, Setting, and Participants This cohort study included females with invasive BC that was newly diagnosed between January 1, 1995, and December 31, 2013, in Finland. The cohort had available hormone receptor data and at least 1 cholesterol measurement. All data were obtained from Finnish national registries. Statistical analyses were performed from January to May 2022. Exposure Use of statins; statin dose; and serum cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels measured separately before and after BC diagnosis. Main Outcomes and Measures Breast cancer mortality and overall mortality between date of BC diagnosis and December 31, 2015. Results A total of 13 378 female patients with BC (median [IQR] age, 62 [54-69] years) participated in the study. The median (IQR) follow-up was 4.5 (2.4-9.8) years after BC diagnosis, during which 16.4% of patients died and 7.0% died of BC. Prediagnostic statin use was a risk factor for BC death even after adjustment for total cholesterol level (hazard ratio [HR], 1.22; 95% CI, 1.02-1.46; P = .03). Reduced risk for BC death was seen for postdiagnostic statin use (HR, 0.85; 95% CI, 0.73-1.00; P = .05). The risk reduction was robust in participants whose cholesterol level decreased after starting statins (HR, 0.49; 95% CI, 0.32-0.75; P = .001) but was nonsignificant if cholesterol level did not subsequently decrease (HR, 0.69; 95% CI, 0.34-1.40; P = .30). Reduced BC mortality among statin users was also observed in females with estrogen receptor–positive tumors (HR, 0.82; 95% CI, 0.68-0.99; P = .03). Overall mortality was lower among statin users vs nonusers when adjusted for serum cholesterol level (HR, 0.80; 95% CI, 0.72-0.88; P &amp;amp;lt; .001). Conclusions and Relevance Results of this cohort study showed that postdiagnostic use of statins was associated with reduced BC mortality compared with nonuse, and the risk was associated with subsequent change in serum cholesterol level. This finding suggests that cholesterol-lowering interventions with statins may be beneficial for patients with BC.
Leveraging Large Language Models for Decision Support in Personalized Oncology
Authors: Manuela Benary, Xing David Wang, Max Schmidt, Dominik Soll, Georg Hilfenhaus, Mani Nassir, Christian Sigler, Maren Knödler, Ulrich Keller, Dieter Beule, Ulrich Keilholz, Ulf Leser, Damian T. Rieke
Journal: JAMA Network Open (2023)

Clinical interpretation of complex biomarkers for precision oncology currently requires manual investigations of previous studies and databases. Conversational large language models (LLMs) might be beneficial as automated tools for assisting clinical decision-making.
Plasma Ceramides and Sphingomyelins and Sudden Cardiac Death in the Cardiovascular Health Study
Authors: Lee B. Bockus, Paul N. Jensen, Amanda M. Fretts, Andrew N. Hoofnagle, Barbara McKnight, Colleen M. Sitlani, David S. Siscovick, Irena B. King, Bruce M. Psaty, Nona Sotoodehnia, Rozenn N. Lemaitre
Journal: JAMA Network Open (2023)

Importance Sphingolipids, including ceramides and sphingomyelins, may influence the pathophysiology and risk of sudden cardiac death (SCD) through multiple biological activities. Whether the length of the fatty acid acylated to plasma sphingolipid species is associated with SCD risk is not known. Objective To determine whether the saturated fatty acid length of plasma ceramides and sphingomyelins influences the association with SCD risk. Design, Setting, and Participants In this cohort study, multivariable Cox proportional hazards regression models were used to examine the association of sphingolipid species with SCD risk. The study population included 4612 participants in the Cardiovascular Health Study followed up prospectively for a median of 10.2 (IQR, 5.5-11.6) years. Baseline data were collected from January 1992 to December 1995 during annual examinations. Data were analyzed from February 11, 2020, to September 9, 2023. Exposures Eight plasma sphingolipid species (4 ceramides and 4 sphingomyelins) with saturated fatty acids of 16, 20, 22, and 24 carbons. Main Outcome and Measure Association of plasma ceramides and sphingomyelins with saturated fatty acids of different lengths with SCD risk. Results Among the 4612 CHS participants included in the analysis (mean [SD] age, 77 [5] years; 2724 [59.1%] women; 6 [0.1%] American Indian; 4 [0.1%] Asian; 718 [15.6%] Black; 3869 [83.9%] White, and 15 [0.3%] Other), 215 SCD cases were identified. In adjusted Cox proportional hazards regression analyses, plasma ceramides and sphingomyelins with palmitic acid (Cer-16 and SM-16) were associated with higher SCD risk per higher SD of log sphingolipid levels (hazard ratio [HR] for Cer-16, 1.34 [95% CI, 1.12-1.59]; HR for SM-16, 1.37 [95% CI, 1.12-1.67]). Associations did not differ by baseline age, sex, race, or body mass index. No significant association of SCD with sphingolipids with very-long-chain saturated fatty acids was observed after correction for multiple testing (HR for ceramide with arachidic acid, 1.06 [95% CI, 0.90-1.24]; HR for ceramide with behenic acid, 0.92 [95% CI, 0.77-1.10]; HR for ceramide with lignoceric acid, 0.92 [95% CI, 0.77-1.09]; HR for sphingomyelin with arachidic acid, 0.83 [95% CI, 0.71-0.98]; HR for sphingomyelin with behenic acid, 0.84 [95% CI, 0.70-1.00]; HR for sphingomyelin with lignoceric acid, 0.86 [95% CI, 0.72-1.03]). Conclusions and Relevance The findings of this large, population-based cohort study of SCD identified that higher plasma levels of Cer-16 and SM-16 were associated with higher risk of SCD. Future studies are needed to examine the underlying mechanism of these associations.
Developing Practical Strategies to Enable Better Teamwork and Communication
Authors: Carl Macrae
Journal: JAMA Network Open (2023)

Becky J. Wong, MD, MSc; Aussama K. Nassar, MD, MSc; Michelle Earley, MS; Ling Chen, MSN, RN, CNOR; Teresa Roman-Micek, BS, CHSOS; Samuel H. Wald, MD, MBA; Tait D. Shanafelt, MD; Sara N. Goldhaber-Fiebert, MD
Abstract 12228: Prognostic Role of Renal Replacement Therapy Among Hospitalized Patients With Heart Failure in the Brazilian National Public Health System
Authors: Andrea Coy-Cangucu, Lígia M Antunes Correa, Marilda Mazzali, Paula Abrao, Fernanda M Mendes, CINTHIA M TEIXEIRA, Karynna P Viana, Guilherme Cordeiro, Maurício Longato, Otávio R Coelho, Jos Souza, Wilson Nadruz, Andrei Sposito, Steffen E Petersen, Michael Jerosch-Herold, Otavio R Coelho-Filho
Journal: Circulation (2023)

Introduction: Data on survival and prognostic factors of patients hospitalized with HF in Brazil are scarce. Aims: To determine the in-hospital all-cause mortality rate, in-hospital renal replacement therapy (RRT) rate, and its association with in-hospital mortality in a population of patients admitted with HF to hospitals from the Brazilian National Public Health System (SUS). Methods: We included adult patients with a documented diagnosis of HF (ICD-10 I50.X) admitted to any public hospital in the SUS Hospital Information System (SIHSUS) registry from April 2017 to August 2021. RRT included intermittent hemodialysis, continuous hemodialysis, and peritoneal dialysis. Descriptive statistics and univariate and multivariate Cox regression were employed. Results: Of the 910,128 HF hospitalizations identified, 106,383 (11.7%) resulted in in-hospital death (Table 1). RRT (required by 8,179 non-survivors [7.7%] and 11,496 survivors [1.4%, p &lt; 0.001]) was associated with a 56% increase in the risk of death (HR 1.56, 95% CI 1.52 - 1.59) (Fig 1). All forms of RRT were independently associated with in-hospital mortality (Fig 2). Female sex (HR 1.04, 95% CI 1.03-1.06) and COVID-19 (HR 1.41, 95% CI 1.14-1.81) were identified as risk factors for in-hospital mortality, while heart transplantation improved survival (HR 0.37, 95% CI 0.29-0.47). Hospitalizations requiring RRT and hospitalizations resulting in death were both longer and costlier (Fig 3, 4). Conclusion: In this nationwide registry of patients admitted with HF to Brazilian public hospitals, we found an alarming mortality rate double the estimates reported in European and North American countries. RRT was strongly associated with a prolonged hospital stay, higher cost-of-hospitalization, and in-hospital death. Our findings highlight the significance of optimizing medical therapy for patients admitted with HF to prevent the deterioration of their renal function and the need for RRT.
The experiential nature of dysphoria: formulating a new conceptual framework following a qualitative study exploring the lives of seven young trans men
Authors: Emily Ryall, Rachael Bullingham, Francesca O’Neil
Journal: International Journal of Transgender Health (2023)

Background 'Gender dysphoria' is commonly used to describe feelings of psychological discomfort, unease, anxiety, or distress in trans individuals. Whilst the past decade has shown a significant rise in research on the experiences of trans individuals in society, the amount of literature dedicated to the experiences of trans men has been much more limited, and particularly research focused on the experiences of young trans men. As such, the range and scope of dysphoric experiences will not have been fully captured and there will be gaps in both general and clinical understanding and conceptualization.
Robotic-assisted laparoscopic colpectomy combined with a hysterectomy and bilateral salpingo-oophorectomy versus a vaginal colpectomy in trans masculine individuals
Authors: Charlotte Nikkels, Asra Vestering, Judith A. F. Huirne, Robert A. de Leeuw, Norah. M. van Mello, Freek A. Groenman
Journal: International Journal of Transgender Health (2023)

Colpectomy entails the surgical removal of the vaginal epithelium. It may be performed in trans-masculine individuals as gender-affirming surgery. Vaginal colpectomy is a complex procedure with potentially severe complications. As alternative, robotic-assisted laparoscopic colpectomy combined with robotic-assisted laparoscopic hysterectomy and possible bilateral salpingo-oophorectomy (RAC+) can be performed.
The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial
Authors: Lindsay B. Kilburn, Dong-Anh Khuong-Quang, Jordan R. Hansford, Daniel Landi, Jasper van der Lugt, Sarah E. S. Leary, Pablo Hernáiz Driever, Simon Bailey, Sébastien Perreault, Geoffrey McCowage, Angela J. Waanders, David S. Ziegler, Olaf Witt, Patricia A. Baxter, Hyoung Jin Kang, Timothy E. Hassall, Jung Woo Han, Darren Hargrave, Andrea T. Franson, Michal Yalon Oren, Helen Toledano, Valérie Larouche, Cassie Kline, Mohamed S. Abdelbaki, Nada Jabado, Nicholas G. Gottardo, Nicolas U. Gerber, Nicholas S. Whipple, Devorah Segal, Susan N. Chi, Liat Oren, Enrica E. K. Tan, Sabine Mueller, Izzy Cornelio, Lisa McLeod, Xin Zhao, Ashley Walter, Daniel Da Costa, Peter Manley, Samuel C. Blackman, Roger J. Packer, Karsten Nysom
Journal: Nature Medicine (2023)

Abstract BRAF genomic alterations are the most common oncogenic drivers in pediatric low-grade glioma (pLGG). Arm 1 ( n = 77) of the ongoing phase 2 FIREFLY-1 (PNOC026) trial investigated the efficacy of the oral, selective, central nervous system–penetrant, type II RAF inhibitor tovorafenib (420 mg m − 2 once weekly; 600 mg maximum) in patients with BRAF -altered, relapsed/refractory pLGG. Arm 2 ( n = 60) is an extension cohort, which provided treatment access for patients with RAF -altered pLGG after arm 1 closure. Based on independent review, according to Response Assessment in Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria, the overall response rate (ORR) of 67% met the arm 1 prespecified primary endpoint; median duration of response (DOR) was 16.6 months; and median time to response (TTR) was 3.0 months (secondary endpoints). Other select arm 1 secondary endpoints included ORR, DOR and TTR as assessed by Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO) criteria and safety (assessed in all treated patients and the primary endpoint for arm 2, n = 137). The ORR according to RAPNO criteria (including minor responses) was 51%; median DOR was 13.8 months; and median TTR was 5.3 months. The most common treatment-related adverse events (TRAEs) were hair color changes (76%), elevated creatine phosphokinase (56%) and anemia (49%). Grade ≥3 TRAEs occurred in 42% of patients. Nine (7%) patients had TRAEs leading to discontinuation of tovorafenib. These data indicate that tovorafenib could be an effective therapy for BRAF -altered, relapsed/refractory pLGG. ClinicalTrials.gov registration: NCT04775485 .
CD97 negatively regulates the innate immune response against RNA viruses by promoting RNF125-mediated RIG-I degradation
Authors: Huasong Chang, Peili Hou, Xuefeng Wang, Aibiao Xiang, Hao Wu, Wenjing Qi, Rukun Yang, Xue Wang, Xingyu Li, Wenqi He, Guimin Zhao, Weiyang Sun, Tiecheng Wang, Daniel Chang He, Hongmei Wang, Yuwei Gao, Hongbin He
Journal: Cellular and Molecular Immunology (2023)
Advancing pathogen genomics in resource-limited settings
Authors: Paul Michael Pronyk, Ruklanthi de Alwis, Rebecca Rockett, Kerri Basile, Yann Felix Boucher, Vincent Pang, October Sessions, Marya Getchell, Tanya Golubchik, Connie Lam, Raymond Lin, Tze-Minn Mak, Ben Marais, Rick Twee-Hee Ong, Hannah Eleanor Clapham, Linfa Wang, Yorin Cahyorini, Francisco Gerardo M. Polotan, Yuni Rukminiati, Eby Sim, Carl Suster, Gavin J.D. Smith, Vitali Sintchenko
Journal: Cell Genomics (2023)

Genomic sequencing has emerged as a powerful tool to enhance early pathogen detection and characterization with implications for public health and clinical decision making. Although widely available in developed countries, the application of pathogen genomics among low-resource, high-disease burden settings remains at an early stage. In these contexts, tailored approaches for integrating pathogen genomics within infectious disease control programs will be essential to optimize cost efficiency and public health impact. We propose a framework for embedding pathogen genomics within national surveillance plans across a spectrum of surveillance and laboratory capacities. We adopt a public health approach to genomics and examine its application to high-priority diseases relevant in resource-limited settings. For each grouping, we assess the value proposition for genomics to inform public health and clinical decision-making, alongside its contribution toward research and development of novel diagnostics, therapeutics, and vaccines.
Biomimetic Nanoarchitectonics with Chitosan Nanogels for Collaborative Induction of Ferroptosis and Anticancer Immunity for Cancer Therapy
Authors: Ning Yang, Xiuhua Pan, Xiawei Zhou, Zengyi Liu, Jie Yang, Jun Zhang, Zengguang Jia, Qi Shen
Journal: Advanced Healthcare Materials (2023)

Abstract Immunogenic cell death (ICD) shows promising therapeutic potential for tumor regression. However, the low sensitivity and immunosuppressive state of current cell death manners seriously impede tumor immunogenicity. Ferroptosis characterized by excessive lipid peroxidation, has emerged as a potential strategy to induce ICD and activate antitumor immune responses. However, the effectiveness of ferroptosis is limited by antioxidant regulatory networks, including the glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) pathways, presenting challenges for its induction. Herein, they propose a novel approach that involves utilizing functionalized chitosan‐ferrocene‐sodium alginate (CFA) crosslinked nanogels, which are modified to pravastatin (PRV) and M1 macrophage membrane (MM) (designing as CFA/PRV@MM). Specifically, ferrocene boots intracellular reactive oxygen species levels for efficient glutathione (GSH) depletion through Fenton reaction, thus disrupting the GPX4/GSH axis, while PRV intervenes in the mevalonate pathway to inhibit the FSP1/CoQ10 antioxidant axis, thereby synergistically causing pronounced ferroptotic damage and promoting ICD. The CFA/PRV@MM nanogels demonstrate superior therapeutic efficacy in a mouse breast model, resulting in effective tumor ablation and immune response with minimal side effects. RNA transcription analysis reveals that nanogels can significantly affect metabolic progress, as well as immune activation. This research provides valuable insights into the design of ferroptosis induction for cancer immunotherapy.
Optimism Surrounds Claudin 18.2 ADC
Journal: Cancer Discovery (2023)

Abstract In a phase I trial of CMG901—a first-in-class antibody–drug conjugate targeting claudin 18.2—researchers found that it can best current therapies for treating gastric and gastroesophageal cancers. Historically, progression-free survival (PFS) hovers around 7 months and overall survival (OS) around 14 to 16 months. However, depending on the dose, PFS with CMG901 ranged from 3.3 to 14.5 months, and OS ranged from 8.5 months to not reached, after a median follow up of 6 months.
Effect of physical activity on risk of Alzheimer's disease: A systematic review and meta-analysis of twenty-nine prospective cohort studies
Authors: Xiaoqian Zhang, Qu Li, Wenqiang Cong, Siyu Mu, Rui Zhan, Shanshan Zhong, Mei Zhao, Chuansheng Zhao, Kexin Kang, Zhike Zhou
Journal: Ageing Research Reviews (2023)
Multidrug-resistant Corynebacterium diphtheriae in people with travel history from West Africa to France, March to September 2023
Authors: Sylvie Brémont, Virginie Passet, Mélanie Hennart, Laure Fonteneau, Julie Toubiana, Edgar Badell, Sylvain Brisse
Journal: Eurosurveillance (2023)

We describe 10 unlinked cases of Corynebacterium diphtheriae infection (nine cutaneous, one respiratory) in France in 2023 in persons travelling from Guinea, Mali, Senegal, Niger or Nigeria and Central African Republic. Four isolates were toxigenic. Seven genomically unrelated isolates were multidrug-resistant, including a toxigenic respiratory isolate with high-level resistance to macrolides and beta-lactams. The high rates of resistance, including against first-line agents, call for further microbiological investigations to guide clinical management and public health response in ongoing West African outbreaks.
Using doxycycline for prophylaxis of bacterial sexually transmitted infections: considerations for the European Union and European Economic Area
Authors: Otilia Mårdh, Diamantis Plachouras
Journal: Eurosurveillance (2023)

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Can physicians and schools mitigate social inequalities in human papillomavirus vaccine awareness, uptake and vaccination intention among adolescents? A cross-sectional study, France, 2021 to 2022
Authors: Hadrien Moffroid, Damien Oudin Doglioni, Sandra Chyderiotis, Jonathan Sicsic, Anne-Sophie Barret, Jocelyn Raude, Sebastien Bruel, Aurelie Gauchet, Morgane Michel, Amandine Gagneux-Brunon, Nathalie Thilly, Judith E Mueller
Journal: Eurosurveillance (2023)

Background In France, human papillomavirus (HPV) vaccination coverage varies across socioeconomic levels. Aim We aimed at assessing HPV vaccine awareness, uptake and vaccination intention among adolescents in France. Methods In a cluster-randomised study, 13–15-year-old students in 61 French middle schools completed a web-based questionnaire. We used multivariable logistic regression to evaluate determinants of HPV vaccine awareness, self-reported uptake and vaccination intention among unvaccinated students and interaction terms to explore effects of visits to family physician and remembering school lessons on vaccination. The French deprivation index of school municipalities served as proxy for socioeconomic levels. Results Among 6,992 participants, awareness was significantly associated with parental education (odds ratio (OR) = 0.82; 95% confidence interval (CI): 0.71–0.95), language spoken at home (OR = 0.59; 95% CI: 0.52–0.66) and deprivation level (OR = 0.57; 95% CI: 0.44–0.71), regardless of physician visit or school lessons. Vaccine uptake was associated with parental education without a recent physician visit (OR = 0.31; 95% CI: 0.16–0.59, vs OR = 0.64; 95% CI: 0.52–0.78 with a visit, interaction p = 0.045). Vaccination intention among unvaccinated was associated with deprivation level (moderate-low vs low) among students not remembering school lessons on vaccination (OR = 0.17; 95% CI: 0.05-0.62, vs OR = 0.93; 95% CI: 0.51–1.67 remembering school lessons, interaction p = 0.022). Parental education was associated with vaccination intention among students reporting a physician visit (OR = 0.41; 95% CI: 0.26–0.64 vs OR = 1.05; 95% CI: 0.50–2.20 without a visit, interaction p = 0.034). Conclusion Our results suggest that healthcare and school could promote vaccination and mitigate social inequalities in HPV vaccination coverage.